Trichosporon beigelii is an opportunistic fungus which is being isolated in recent years from fatal septicemic infections in immunocompromised patients, particularly in those with cancer and granulocytopenia. Serodiagnosis of this condition is often made using a cryptococcal latex agglutination test, because of the cross-reaction between a cell wall polysaccharide antigen of T. beigelii and the capsular glucuronoxylomannan of Cryptococcus neoformans, another fatal opportunistic fungal pathogen. We isolated, purified and immunochemically characterized the cross-reactive T. beigelii polysaccharide. Its repeat unit consists of mannose, xylose, glucuronic acid and glucose; the polysaccharide is O-acetylated. We also perfirmed a comparative quantitation of this polysaccharide in clinical and non- clinical isolates of T. beigelii recovered from different parts of the U.S. using rocket immunoelectrophoresis. Both clinical and non-clinical strains produced the polysaccharide in vitro; significantly higher quantity of the polysaccharide was released by the deep isolates than by superficial isolates.C. neoformans is an invasive fungal pathogen and the capsular glucuronoxylomannan (GXM) of all serotypes of C. neorormans are O-acetylated, whereas that of less virulent cryptococci such as C. laurentii and C. albidus are non-O-acetylated. Using an immunodot technique and an O-acetyl-specific cryptococcal antiserum, we found a significantly higher percentage (89%) of deep isolates of T. beigelii produce O-acetylated polysaccharide, compared to only 17% of superficial isolates. Thus, the cross-reactive polysaccharide antigen of T. beigilii serves as a diagnostic marker and may play a role in pathogenesis.